Understanding competitive adsorption behaviors and pore-filling mechanisms of multicomponent gas mixtures in metal–organic frameworks (MOFs) is essential for advancing gas separation technologies. This study explores the adsorption dynamics of CO2, CH4, and N2 in MIL-101(Cr), demonstrating how its unique topological structure determines adsorption capacity and governs competitive interactions. Pure CO2 and N2 exhibit edge-to-center pore-filling sequences, while CH4 fills from the center outward. In mixed gas systems, CH4 dominates by reshaping the spatial distribution and filling sequence of CO2 and N2, while its own adsorption remains stable. Excess CO2 or CH4 inhibits competing gases from accessing adsorption sites, whereas excess N2 enhances CH4 adsorption, revealing a nuanced interplay of competitive effects. Furthermore, these interactions influence gas mobility, with excess molecules reducing the self-diffusion coefficients of other gases while increasing their own. This work also introduces a novel computational framework that integrates molecular-scale simulations with process-scale modelling to predict breakthrough curves of gas mixtures with high accuracy. The proposed two-stage adsorption process highlights MIL-101(Cr)’s exceptional potential for purifying CH4 from coal bed methane and biogas under ambient conditions. These findings underscore the utility of MIL-101(Cr) and computational innovations for sustainable energy applications and greenhouse gas mitigation.